Normal adult human tissues and cultured bronchial epithelial cells and fibroblasts exhibit 06-alkylguanine-DNA alkyltransferase activity in vitro by catalyzing the repair of the promutagenic alkyltransferase activity in vitro by catalyzing the repair of the promutagenic alkylation lesion 06-methylguanine from DNA. Alkyl-transferase activity varies in the different human tissues tested in the decreasing order of liver, colon, esophagus, peripheral lung and brain. Formaldehyde inhibits repair of 06-methylguanine and potentiates the mutagenicity of an alkylating agent, N-methyl-N-nitrosourea, in normal human fibroblasts. In some experimental studies, repeated exposure to alkylating agents has led to an increase in 06-methylguanine- DNA alkyltransferase activity, i.e., an adaptive response. We have shown that human bronchial epithelial cells do not adapt and increase their DNA repair capability. This finding has important implications in carcinogenesis caused by low doses of N-nitrosamines. The effects of cigarette smoke condensate, catechol and smoke "conditioned" media on the activity of 06- methylguanine-DNA alkyltransferase (06MT) and uracil-DNA glycosylase (UDG) on cultured human bronchial epithelial cells, HUT 292 cells and Beas-12 cells is currently under investigation. The activity of these two DNA repair enzymes is also being measured in the alveolar macrophages and peripheral blood lymphocytes of smokers and nonsmokers. Interindividual and intraindividual variation in these activities is up to 100-fold and 6-fold, respectively. Preliminary results indicate a significant rise in UDG activity in the macrophages of smokers compared to nonsmokers.